前列腺癌术前新辅助治疗的研究进展

根治性前列腺切除术是治疗局限性前列腺癌的重要方法,但前列腺癌患者术前准确临床分期较困难,常出现肿瘤切除不彻底、术后肿瘤易复发和转移.研究证实术前新辅助内分泌治疗(NHT)能缩小前列腺体积,降低PSA水平,降低手术切缘阳性率,但精囊受侵率及盆腔淋巴结转移无减少,未发现无PSA进展率及肿瘤特异性生存率方面的优势.目前的资料尚不能证实所有患者术前都必须进行新辅助内分泌治疗.     

多学科综合治疗——改善高危前列腺癌患者的预后

手术和放疗是局限性前列腺癌主要的治疗方法,但对于高危前列腺癌单用局部治疗预后不佳,超过50％的患者会复发。手术、放疗、内分泌治疗和化疗的联合应用目前被认为是提高高危前列腺癌疗效的重要途径。本文总结了目前高危前列腺癌综合治疗的相关文献,期望能为我国高危前列腺癌综合治疗方案的选择提供借鉴和参考。     

Clinical Analysis of Perioperative Outcomes on Neoadjuvant Hormone Therapy before Laparoscopic and Robot-Assisted Surgery for Localized High-Risk Prostate Cancer in a Chinese Cohort

Objective: To analyze the perioperative outcomes of neoadjuvant hormone therapy (NHT) before laparoscopic and robot-assisted surgery for localized high-risk prostate cancer in a Chinese cohort. Methods: The clinical data of 385 patients with localized high-risk prostate cancer who underwent radical prostatectomy (RP) in our hospital from January 2019 to June 2021 were analyzed retrospectively, including 168 patients with preoperative NHT and 217 patients with simple surgery. Clinical characteristics were compared in the above two groups, the laparoscopic RP (LRP) cohort (n = 234) and the robot-assisted laparoscopic radical prostatectomy (RALP) cohort (n = 151), respectively. Results: In the overall cohort, compared with the control group, the NHT group had a shorter operative time, less blood loss, a lower positive surgical margin rate, and a higher proportion of Gleason score (GS) downgrading after the operation (p < 0.05). However, there was no significant difference in hospitalization time, biochemical recurrence, urine leakage, urinary continence, or prostate-specific antigen (PSA) progression-free survival (p > 0.05). In the LRP cohort, it was found that the NHT group also had shorter operative time, less blood loss, lower positive surgical margin rate, a higher proportion of GS downgrading after the operation, and faster recovery of urinary control than the control group (p < 0.05). There was no marked difference in hospitalization time, biochemical recurrence, urinary leakage, or PSA progression-free survival. However, in the RALP cohort, the NHT group had a significant difference in the GS downgrading after the operation compared with the control group (p < 0.05). In the overall cohort, multiple analyses showed that initial PSA level, GS at biopsy, clinical T stage, lymph node invasion, use of NHT, and surgical methods were significantly associated with positive surgical margin (p < 0.05) while NHT did not account for biochemical recurrence (p > 0.05). Conclusions: NHT can lower the difficulty of surgery, reduce positive surgical margin rate, and help recovery in short-term urinary control in patients with high-risk prostate cancer after LRP. However, we do not have evidence on the benefit of NHT in high-risk PCa patients treated with RALP. For these patients, surgery can be performed as early as possible.     

Contemporary treatment of high-risk localized prostate cancer

High-risk prostate cancer poses a significant challenge to the treating physician and much debate exists regarding the ideal treatment approach. The purpose of this article is to enable physicians to identify patients with high-risk localized prostate cancer and evaluate whether monotherapy is sufficient for these patients. We review the current data on use of surgery, radiation therapy and hormonal therapy independently and in combination. We also discuss emerging therapeutics for high-risk disease including neoadjuvant chemotherapy and protocols under current and future investigation.     

前列腺干细胞抗原在前列腺癌诊断与治疗中的应用

人们对前列腺癌理想的诊断和治疗方式的探寻从未停止.近些年来,随着对前列腺干细胞抗原(prostate stem cell antigen,PSCA)研究地不断深入,特别是应用于前列腺癌诊治方面的新成果不断推出,使人们对PSCA充满期望.本文重点对PSCA的生物学特性及其在前列腺癌诊断方法和免疫治疗方面的新进展进行综述.     

Phase II trial of short-term neoadjuvant docetaxel and complete androgen blockade in high-risk prostate cancer

Background:

The low probability of curing high-risk prostate cancer (PC) with local therapy suggests the need to study modality of therapeutic approaches. To this end, a prospective phase II trial of neoadjuvant docetaxel (D) and complete androgen blockade (CAB) was carried out in high-risk PC patients. The primary end point was to detect at least 10% of pCRs after chemohormonal treatment.

Methods:

Patients with T1c–T2 clinical stage with prostate-specific antigen (PSA) >20 ng ml⁻¹ and/or Gleason score ⩾7 (4+3) and T3 were included. Treatment consisted of three cycles of D 36 mg m⁻² on days 1, 8 and 15 every 28 days concomitant with CAB, followed by radical prostatectomy (RP).

Results:

A total of 57 patients were included. Clinical stage was T1c, 11 patients (19.3%); T2, 30 (52.6%) and T3, 16 (28%) patients. Gleason score was ⩾7 (4+3) in 44 (77%) patients and PSA >20 ng ml⁻¹ in 15 (26%) patients. Treatment was well tolerated with 51 (89.9%) patients completing neoadjuvant therapy together with RP. The rate of pCR was 6% (three patients). Three (6%) additional patients had microscopic residual tumour (near pCR) in prostate specimen. With a median follow-up of 35 months, 18 (31.6%) patients presented PSA relapse.

Conclusion:

Short-term neoadjuvant D and CAB induced a 6% pCR rate, which is close to what would be expected with ADT alone. The combination was generally well tolerated.     

Key papers in prostate cancer

Prostate cancer is the most common cancer and second leading cause of death in men. The evidence base for the diagnosis and treatment of prostate cancer is continually changing. We aim to review and discuss past and contemporary papers on these topics to provoke debate and highlight key dilemmas faced by the urological community. We review key papers on prostate-specific antigen screening, radical prostatectomy versus surveillance strategies, targeted therapies, timing of radiotherapy and alternative anti-androgen therapeutics. Previously, the majority of patients, irrespective of risk, underwent radical open surgical procedures associated with considerable morbidity and mortality. Evidence is emerging that not all prostate cancers are alike and that low-grade disease can be safely managed by surveillance strategies and localized treatment to the prostate. The question remains as to how to accurately stage the disease and ultimately choose which treatment pathway to follow.     

Twenty‐four‐month postradiation prostate biopsies are strongly predictive of 7‐year disease‐free survival

BACKGROUND:

The objective of this study was to evaluate the predictive value of prostate biopsies that were obtained 24 months after the completion of radiotherapy (RT) with respect to disease‐free survival (DFS) in a randomized trial that compared 3 months versus 8 months of neoadjuvant hormone therapy before conventional dose external RT.

METHODS:

From February 1995 to June 2001, 378 men were randomized to receive either 3 months or 8 months of combined flutamide and goserelin before they received 66 Gray of RT at 4 participating centers. By risk group, 26% of patients were categorized as low risk, 43% were categorized as intermediate risk, and 31% were categorized as high risk. The 2 treatment arms were balanced in terms of age, Gleason score, clinical tumor classification, risk group, and presenting prostate‐specific antigen level. The median follow‐up for the patients who remained alive was 6.6 years (range, 1.6‐10.1 years). Of 361 evaluable patients, 290 patients remained alive. Post‐RT prostate biopsies were performed between 24 and 30 months after the completion of RT in 3 of the 4 centers. Biopsies that had residual tumor with severe treatment effect were considered indeterminate, and biopsies that had minimal or no treatment effect were considered positive.

RESULTS:

The 5‐year rate of actuarial freedom from any failure for the 3‐month arm versus the 8‐month arm was 72% versus 75% (P = .18). The DFS for patients who had negative and indeterminate biopsies was similar. Two‐year post‐treatment biopsy status was a strong predictor of 5‐year DFS rate (82% and 83% for negative and indeterminate biopsies, respectively, vs 27% for positive biopsies; P < .0001). Multivariate analysis indicated that biopsy status (P < .0001) and Gleason score (P < .0001) were the strongest determinates of biochemical DFS.

CONCLUSIONS:

Two‐year post‐RT prostate biopsies were strongly predictive of subsequent DFS. Biopsies with severe treatment effect were considered negative. Cancer 2009. © 2008 American Cancer Society.     

Neoadjuvant therapy preceding prostatectomy for prostate cancer: rationale and current trials

Neoadjuvant therapy improves outcomes for a number of malignancies and provides intermediate pathologic outcomes, which correlate with long-term outcomes. Neoadjuvant androgen-deprivation therapy, alone or with docetaxel chemotherapy, preceding prostatectomy for localized prostate cancer is feasible and demonstrates pathologic activity, but evidence for improved long-term outcomes is lacking. Data in support of the further exploration of neoadjuvant therapy for localized prostate cancer preceding prostatectomy are reviewed. Ongoing randomized trials are elucidating the impact of neoadjuvant androgen deprivation combined with docetaxel chemotherapy on pathologic and long-term outcomes. The correlation of pathologic and biologic outcomes with long-term outcomes in this setting is unknown. The neoadjuvant therapy approach followed by prostatectomy is feasible with a wide array of agents and provides a paradigm for evaluating the activity, and mechanism of action and resistance to new treatments. This promising modality may aid the rapid development of novel therapeutic agents. A multidisciplinary approach involving oncologists, urologists and pathologists is critical to the success of this model.     

Role of radiotherapy in ductal (endometrioid) carcinoma of the prostate

BACKGROUND: Ductal carcinoma of the prostate is a rare variant of prostate cancer that presents most commonly with obstructive urinary symptoms or hematuria. This case series of 6 patients is the first to report the outcome of ductal carcinoma treated with external beam radiotherapy. METHODS: A retrospective review was performed of patients treated between 1980 and 2006 at Fox Chase Cancer Center, Philadelphia, Penn. Six patients were identified with ductal carcinoma. RESULTS: Five of the 6 patients were treated definitively and the sixth patient was treated at recurrence 3 years after a radical prostatectomy. Patient ages ranged from 66-80 years and the initial prostate-specific antigen (iPSA) ranged from 1.69-100.3 ng/mL. Three patients had a mixed acinar and ductal carcinoma, 2 with a Gleason score (GS) of 8 and 1 with a GS of 7. Of the patients treated definitively, 4 had clinical stage T2A-T2C and 1 had clinical stage T1B. Definitive radiotherapy was delivered to the prostate with doses between 72 Gy and 78 Gy. Pelvic lymph nodes were treated in all patients. One patient was treated postradical prostatectomy to the prostate bed to a dose of 60 Gy. Adjuvant androgen deprivation was given in 5 of the patients. Two of the patients died from metastatic disease at 1.4 and 7.1 years after treatment. The remaining 4 patients remain alive between 3.2 and 4.8 years from treatment, with 3 patients biochemically without evidence of disease. No patients have developed a local recurrence. CONCLUSIONS: Ductal carcinoma of the prostate may be treated effectively with external beam radiotherapy. Aggressive management is indicated, even with low-volume metastatic disease.     

Neoadjuvant therapy followed by prostatectomy for clinically localized prostate cancer

The results of this assessment of the literature indicated that neoadjuvant therapy followed by prostatectomy may improve long-term outcomes for patients with high-risk localized disease. In addition, this approach provides a paradigm for evaluating the activity and mechanism of action of new agents as correlative studies are facilitated by the availability of tumor tissue before and after therapy. The authors determined that a multidisciplinary approach involving oncologists, urologists, and pathologists is critical to the success of this model. Recent and ongoing studies of neoadjuvant therapy followed by prostatectomy were reviewed.     

Management of prostate cancer recurrences after radiation therapy-brachytherapy as a salvage option

Depending on initial prognostic factors, an estimated 10%-60% of men who undergo definitive radiation therapy for prostate cancer may experience a biochemical recurrence. Even though hormonal therapy is standard for metastatic recurrences, no consensus exists on optimal salvage therapy for those recurrences thought confined to the prostate. Salvage treatment options for these local recurrences have historically been limited to salvage prostatectomy, hormonal therapy, or cryotherapy. Salvage prostate brachytherapy, however, uses a widely available technique and may provide another option for attaining disease control in patients with localized failures, although only about 110 cases have been reported in the literature. In this report, the authors have described their own series of salvage brachytherapy cases as well as presented a review of other such series reported in the literature. In addition, the authors included a comprehensive review of published experiences with surgery and cryotherapy as salvage options. It appears that salvage brachytherapy, when combined with careful patient selection, is at least as effective as other salvage options with comparable or potentially fewer treatment-related side effects.     

Quality of life after surgery, external beam irradiation, or brachytherapy for early-stage prostate cancer

BACKGROUND: The primary treatments for clinically localized prostate cancer confer equivalent cancer control for most patients but disparate side effects. In the current study, the authors sought to compare health-related quality of life (HRQOL) outcomes after the most commonly used treatments. METHODS: A total of 580 men completed the Medical Outcomes Study Short Form-36, the University of California-Los Angeles (UCLA) Prostate Cancer Index, and the American Urological Association Symptom Index before and through 24 months after treatment with radical prostatectomy (RP), external beam radiation therapy (EBRT), or brachytherapy (BT). RESULTS: General HRQOL did not appear to be affected by treatment. Obstructive and irritative urinary symptoms were more common after BT (P<.001). Urinary control and sexual function were better after EBRT than BT (P<.001 and P=.02, respectively) and better after BT than RP (P<.001 and P=.01, respectively). Among potent men, recovery of sexual function was best after EBRT and was equivalent after bilateral nerve-sparing surgery or BT. Sexual bother was more common than urinary or bowel bother after all 3 treatments. Bowel dysfunction was more common after EBRT or BT than RP (P<.001). CONCLUSIONS: In the current study, treatment for localized prostate cancer was found to differentially affect HRQOL outcomes. Urinary control and sexual function were better after EBRT, although bilateral nerve-sparing surgery diminished these differences among potent men undergoing RP. BT caused more obstructive and irritative symptoms, while both forms of radiation caused more bowel dysfunction. These results may inform medical decision-making in men with localized prostate cancer.     

Analysis of iodine-125 interstitial therapy in the treatment of localized carcinoma of the prostate

Definitive treatment of localized carcinoma of the prostate has included radical surgery, external beam radiation therapy, and interstitial radiation therapy. The interstitial agent most commonly used is Iodine-125. Forty-eight patients were treated with interstitial radiation therapy using Iodine-125 implants with a median follow-up of 55 months. Forty-three percent of the evaluable patients had progressive disease with approximately 50% progressing at 5 years by Kaplan-Meier analysis. Overall actuarial survival in the group was 80% at 5 years. This and several other studies suggest that control of prostate cancer with Iodine-125 seeds may be suboptimal as compared with other treatment modalities, especially the radical retropubic prostatectomy. Analysis of treatment parameters is presented along with a discussion of the current status and future prospects for treatment of localized carcinoma of the prostate with interstitial radiation therapy.     

Secondary bladder cancer after anticancer therapy for prostate cancer: reduced comorbidity after androgen-deprivation therapy

Radiotherapy for prostate cancer is associated with an increased incidence of secondary bladder cancer (BC). We investigated the incidence, clinicopathological characteristics, and prognosis of BC after radiotherapy, surgical therapy, and primary androgen-deprivation therapy (ADT) for prostate cancer. This study included 1,334 Japanese patients with prostate cancer treated with radiotherapy (n=631), surgical therapy (n=437), and primary ADT (n=266). During the median follow-up period of 51.2, 44.8, and 45.5 months, secondary BC occurred in 14 (2.2%), 5 (1.1%), and 0 (0%) of patients with prostate cancer treated with radiotherapy, surgical therapy, and primary ADT, respectively. The 10-year BC-free survival rate was 91.3% in the radiotherapy group, 97.4% in the surgical therapy group, and 100% in the primary ADT group. The rates of intravesical recurrence, progression to muscle-invasive BC, and BC-specific death might be higher in secondary BC after radiotherapy compared with after surgical therapy. There was a significant difference in the incidence of secondary BC among different therapeutic modalities for prostate cancer in Japanese men, indicating significantly lower comorbidity rates of secondary BC after primary ADT for prostate cancer compared with radiotherapy.     

Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer

BACKGROUND:

The long‐term survival of patients with high‐risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen‐deprivation therapy (ADT).

METHODS:

In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate‐specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow‐up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer‐specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk‐regression model.

RESULTS:

The 10‐year cancer‐specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51‐1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68‐1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all‐cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25‐2.05; P = .0002).

CONCLUSIONS:

RRP alone and EBRT plus ADT provided similar long‐term cancer control for patients with high‐risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality‐of‐life and noncancer mortality will be necessary to determine the optimal management approach for these patients. Cancer 2011. © 2011 American Cancer Society.     

Additional therapy for high-risk prostate cancer treated with surgery: what is the evidence?

Single-modality approaches to the treatment of high-risk prostate cancer, whether radical prostatectomy or external-beam radiotherapy, have yielded disappointing results. Treatment intensification has, thus, been the subject of considerable research activity in recent years. This review will discuss the evidence for neoadjuvant and adjuvant treatment approaches when surgery is chosen as the definitive therapy for high-risk prostate cancer. Particular emphasis will be placed on the randomized trials, both completed and in progress. Trials investigating adjuvant radiotherapy, androgen-deprivation therapy and chemotherapy will each be discussed in turn. Among these, only adjuvant radiotherapy has been shown to prolong survival after surgery, and the recently published evidence for this benefit will be discussed in detail.